nature publishing group Review Multimodality neuromonitoring in severe pediatric traumatic brain injury Adam M.H. Young1, Mathew R. Guilfoyle1, Joseph Donnelly1, Peter Smielewski1, Shruti Agarwal2, Marek Czosnyka1 and Peter J. Hutchinson1 Each year, the annual hospitalization rates of traumatic brain the use of cerebral microdialysis studies (2,3). This self- injury (TBI) in children in the United States are 57.7 per 100K in escalating process is further complicated by the presence of the o5 years of age and 23.1 per 100K in the 5–14 years age other organ injuries that cause instability of ventilation and group. Despite this, little is known about the pathophysiology circulation. The intensive management of an infant or child of TBI in children and how to manage it most effectively. with TBI thus involves careful monitoring and manipulation Historically, TBI management has been guided by clinical of the factors that affect oxygen delivery to the brain: blood examination. This has been assisted progressively by clinical gas tensions, blood pressure, ICP, fluid balance, blood imaging, intracranial pressure (ICP) monitoring, and finally a viscosity, and hematocrit; however, there is very little evidence software that can calculate optimal brain physiology. Multi- available to direct optimal patient care in children. Optimiza- modality monitoring affords clinicians an early indication of tion and individualization of intensive care after TBI is the secondary insults to the recovering brain including raised ICP goal of multimodality neurologic monitoring. and decreased cerebral perfusion pressure. From variables Detection of secondary events (such as intracranial such as ICP and arterial blood pressure, correlations can be hypertension, ischemia, worsening edema, excitotoxicity, drawn to determine parameters of cerebral autoregulation seizure, or spreading depressions) remains a major target of (pressure reactivity index) and “optimal cerebral perfusion neuromonitoring and an area of ongoing research. ICP and ” pressure at which the vasculature is most reactive. More CPP are the most widely accepted neuromonitoring para- recently, significant advances using both direct and near- meters and have been shown in many studies to be related to – infrared spectroscopy derived brain oxygenation plus cere- mortality after TBI; however, these studies were specifically bral microdialysis to drive management have been described. adult studies (4–6). More recently, studies in adult patients Here in, we provide a perspective on the state-of-the-art demonstrated that cerebral autoregulation (7,8) and brain techniques recently implemented in clinical practice for tissue oximetry (9–12) have been linked to outcome after head pediatric TBI. injury. Although there is no conclusive proof that optimiza- tion of these parameters may influence neurological recovery, indirect evidence of better outcomes in adults managed in specialized neurocritical care units (13,14), where tiered he early management phase of traumatic brain injury therapy is based on neuromonitoring, supports their use, (TBI) aims to achieve hemodynamic stability, limit T and further exploration of their clinical value within a secondary insults (e.g., hypotension, hypoxia), obtain accurate pediatric cohort. Pineda et al. (15) support the concept that a neurological assessment, and appropriately select patients for pediatric neurocritical care programme can improve the further investigation (1). The primary brain injury leads to outcome in children who sustain a TBI. Direct monitoring of brain edema, elevated intracranial pressure (ICP), and cerebral extracellular chemistry by microdialysis is a promis- disruption of cerebral autoregulation that can lead to ing technique that has enhanced our understanding of the hyperperfusion and worsening edema or hypoperfusion and pathophysiology of brain injury and is maturing as a clinical ischemia. Our understanding of how escalating brain edema monitor that can be employed in combination with other leads to an increase in ICP, which, in turn, causes reduction in monitoring methods (such as cerebral oximetry and ICP cerebral perfusion pressure (CPP; mean arterial blood monitoring) to assist in the management of patients on an pressure minus ICP), cerebral blood flow (CBF), and individual intention-to-treat basis (16,17). Furthermore, the oxygenation, has improved greatly over the past few years implications with regards to pediatric studies may be different (2). Moreover, how these changes impact on cellular in the sense that we have no knowledge of the evolution of the metabolism in the adult brain has been described through inflammatory/metabolic burden in children after injury, 1Department of Clinical Neurosciences, Division of Academic Neurosurgery, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK; 2Department of Pediatric intensive Care, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK. Correspondence: Adam M.H. Young ([email protected]) Received 22 July 2016; accepted 31 August 2017; advance online publication 20 December 2017. doi:10.1038/pr.2017.215 Copyright © 2018 International Pediatric Research Foundation, Inc. Volume 83 | Number 1 | January 2018 Pediatric RESEARCH 41 Review | Young et al. despite accounting for up to 35% of head injuries in pediatric on. Repeating a CT scan in children with severe TBI is usually patients (18). Non-accidental head injury is more closely considered when there is (1) no evidence of neurologic linked with repeated injuries to the brain (19). As a result, the improvement; (2) persistent or increasing ICP; or (3) an pathophysiology of the disease and indeed the treatment of inability to assess neurologic status (e.g., sedation, paralytic non-accidental TBI is different to single injury, high impact agents) (23). Studies have reported delayed or progressive trauma. For these reasons it is excluded from this review as it lesions in 1 to 50% of adult/pediatric patients with TBI (24). is regarded as a different mechanism of injury and less Because epidural hematoma/subdural hematoma requiring frequently are these patients as dependent on high-frequency surgical intervention can develop hours to days after the acute monitoring. injury, some investigators have suggested that a follow-up CT scan be routinely acquired at 1–3 days post injury even when NEUROIMAGING clinical deterioration is not evident under the assumption that The use of neuroimaging has become increasingly valuable in early diagnosis prompts early intervention leading to a better predicting prognosis in severe pediatric TBI, particularly in long-term outcome (25). However, because children with the initial hours post ictus (20). Computed tomography (CT) severe TBI are medically unstable and (if portable CT is not is important for the rapid detection of different types of available) may further deteriorate during transport to the CT intracranial injury including extra-axial hemorrhage (e.g., scanner (hemodynamic instability, increased ICP, oxygen subdural or epidural hematoma), acute hydrocephalus, desaturation), the decision to order a repeat scan is a fractures, or other intracranial lesions that may require acute treatment decision, weighing the knowledge gained against neurosurgical intervention. The early CT is also useful for the risk of additional secondary brain injury. Likewise, triage of patients to detect those who are likely to need because of the long-term effects of CT radiation exposure neurosurgery, require management in an intensive care unit (lifetime risk of fatal cancer resulting from one head CT in a vs. general hospital setting as well as those who can be safely 1-year-old child is as high as 1 in 1,500), the neurosurgical discharged from the emergency department and managed decision to order a CT scan also should be considered a at home. treatment decision, weighing the knowledge gained against It is understood that acute CT imaging is universally the risk of long-term radiation exposure (25). This guideline performed in the developed world for patients with severe addressed the issue of the value of routinely acquiring repeat TBI. Two studies (21,22) show that children with severe TBI CT scans in children with severe TBI. have a high incidence of intracranial injury on CT scan (75% Although magnetic resonance imaging sensitivity is under- and 62%, respectively). In these studies, intracranial injury stood to be superior to CT for intracranial evaluation, it is not included brain contusion, extracerebral hematoma, intracer- as easily obtained acutely after injury and has not been as ebral hematoma, diffuse axonal injury, acute brain swelling, widely validated in large studies, particularly regarding penetrating craniocerebral injury, pneumocephalus, subar- influence on management decisions. Nevertheless, recent achnoid hemorrhage, alterations to cisterns, midline shift, or advances in rapid magnetic resonance imaging has demon- fractures (Figure 1). Neither study included treatment-related strated comparable results to CT (26,27) without the concerns outcome data related to the findings on CT scan and thus over radiation. In addition, particular sequences can be used could not be used as specific evidence for this guideline. to provide correlations with intracranial variables. Specifically, Although CT is always obtained acutely in patients with arterial spin labeling can be used to determine CBF in severe TBI, the use of two or more CT studies is not agreed children (28); however, these are